This program targets a one-year biodegradable estrogen/progestin implant for postmenopausal hormone replacement therapy. Estradiol plus levonorgestrel will be incorporated into an innovative implant design already being developed by BIOTEK for delivery of pure levonorgestrel as a maintenance contraceptive. The implant consists of a drug-free, biodegradable polymer core surrounded by a drug-containing shell, which provides efficient drug delivery. Such implants will biodegrade if left in place for more than a year, yet they can be surgically removed before the end of a year if necessary. With no need to keep track of daily pills or weekly patches, and with little reason to fear an unpleasant removal episode, such implants should provide a welcome new form of sustained hormone replacement therapy. Phase I demonstrated the feasibility of delivering estradiol and levonorgestrel at acceptable rates from the same implants. Phase II will now modify the core polymer to accelerate degradation, improve production methods, characterize promising designs in vitro, and confirm performance in rabbits. PROPOSED COMMERCIAL APPLICATION: The proposed work should lead to the development of a new kind of long lasting, highly effective, biodegradable drug delivery implant. Once fully impemented, implants of similar design should be useful for many other kinds of drug maintenance therapy.